Chromosome 11p15.5 regional imprinting: comparative analysis of KIP2 and H19 in human tissues and Wilms' tumors.

Abstract

The imprinted H19 gene is frequently inactivated in Wilms' tumors (WTs) either by chromosome 11p15.5 loss of heterozygosity (LOH) or by hypermethylation of the maternal allele and it is possible that there might be coordinate disruption of imprinting of multiple 11p15.5 genes in these tumors. To test this we have characterized total and allele-specific mRNA expression levels and DNA methylation of the 11p15.5 KIP2 gene in normal human tissues, WTs and embryonal rhabdomyosarcoma (RMS). Both KIP2 alleles are expressed but there is a bias with the maternal allele contributing 70-90% of mRNA. Tumors with LOH show moderate to marked reductions in KIP2 mRNA relative to control tissues and residual mRNA expression is from the imprinted paternal allele. Among WTs without LOH most cases with H19 inactivation also have reduced KIP2 expression and most cases with persistent H19 expression have high levels of KIP2 mRNA. In contrast to the extensive hypermethylation of the imprinted H19 allele, both KIP2 alleles are hypomethylated and WTs with biallelic H19 hypermethylation lack comparable hypermethylation of KIP2 DNA. 5-aza-2'-deoxycytidine (aza-C) increases H19 expression in RD RMS cells but does not activate KIP2 expression. These data indicate coordinately reduced expression of two linked paternally imprinted genes in most WTs and also suggest mechanistic differences in the maintenance of imprinting at these two loci.

• Authors: W Y Chung, L Yuan, L Feng, T Hensle, B Tycko
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 5 Issue 8 Pg. 1101-8 (Aug 1996) ISSN: 0964-6906 [Print] England
• PMID: 8842727 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CDKN1C protein, human
• Cyclin-Dependent Kinase Inhibitor p57
• DNA Primers
• Enzyme Inhibitors
• H19 long non-coding RNA
• Muscle Proteins
• Nuclear Proteins
• RNA, Long Noncoding
• RNA, Messenger
• RNA, Untranslated
• Decitabine
• DNA Modification Methylases
• Azacitidine

Topics

• Adult
• Alleles
• Azacitidine (analogs & derivatives, pharmacology)
• Base Sequence
• Cell Line
• Child
• Chromosomes, Human, Pair 11 (genetics)
• Cyclin-Dependent Kinase Inhibitor p57
• DNA Methylation
• DNA Modification Methylases (antagonists & inhibitors)
• DNA Primers (genetics)
• Decitabine
• Enzyme Inhibitors (pharmacology)
• Female
• Fetus
• Gene Expression Regulation (drug effects)
• Genes, Tumor Suppressor (drug effects)
• Genomic Imprinting
• Heterozygote
• Humans
• Infant, Newborn
• Kidney Neoplasms (genetics)
• Male
• Muscle Proteins (genetics)
• Nuclear Proteins (genetics)
• RNA, Long Noncoding
• RNA, Messenger (biosynthesis, genetics)
• RNA, Untranslated
• Wilms Tumor (genetics)